title: DISC1-kendrin interaction is involved in centrosomal microtubule network formation.
abstract: Disrupted-In-Schizophrenia 1 (DISC1) was identified as a novel gene disrupted by a (1;11)(q42.1;q14.3) translocation segregating with schizophrenia, bipolar disorder and other major mental illnesses in a Scottish family. We previously identified 446-533 amino acids of DISC1 as the kendrin-binding region by means of a directed yeast two-hybrid interaction assay and showed that the DISC1-kendrin interaction is indispensable for the centrosomal localization of DISC1. In this study, to confirm the DISC1-kendrin interaction, we examined the interaction between deletion mutants of DISC1 and kendrin. Then, we demonstrated that the carboxy-terminus of DISC1 is indispensable for the interaction with kendrin. Furthermore, the immunocytochemistry revealed that the carboxy-terminus of DISC1 is also required for the centrosomal targeting of DISC1. Overexpression of the DISC1-binding region of kendrin or the DISC1 deletion mutant lacking the kendrin-binding region impairs the microtubule organization. These findings suggest that the DISC1-kendrin interaction plays a key role in the microtubule dynamics.
authors.affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Shimizu
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Matsuzaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Hattori
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kumamoto
authors.forename: Ko
authors.initials: K
authors.lastname: Miyoshi
authors.forename: Taiichi
authors.initials: T
authors.lastname: Katayama
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D019556:COS Cells; D002148:Calmodulin-Binding Proteins / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism* / Q000648:ultrastructure; D002522:Chlorocebus aethiops; D006801:Humans; D047468:Immunoprecipitation; D008870:Microtubules / Q000378:metabolism* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion
chemical_list: D002148:Calmodulin-Binding Proteins; C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; C410004:kendrin